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Emerging Concepts in Ion Channel Biophysics
Poster Abstracts
91
3-POS
Board 3
Monoterpenes are Powerful K2P Channels Regulators
Eden Arazi
1,2
, Noam Zilberberg
1,2
.
1
Ben-Gurion University Of The Negev, Beer-Sheva, Israel,
2
Zlotowski Center for Neuroscience,
Beer-Sheva, Israel.
Two pore domain potassium channels (K2P) display constant conductance in the physiological
membrane potential range and their activity is highly regulated by both chemical and physical
modulators. K2P channels' activity affect numerous physiological processes such as cardiac
function, pain perception, depression, neuroprotection and cancer development. Terpenes are a
large family of membrane soluble compounds, mostly produced in plants. Several monoterpenes
were found to affect the activity of a variety of ion channels. To date, the effect of terpenes on
K2P channels has not been studied.
Here we report that terpenes are powerful K2P channel regulators. Human channels were
expressed in Xenopus oocytes and currents were measured using the two-electrode voltage
clamp technique. Channels' activity was found to be highly affected by monoterpenes. For
instance, K2P2.1 and other mechanosensitive K2P channels currents were enhanced several-fold
by carvacrol, thymol and menthol and decreased two-fold by eugenol. The effect of
monoterpenes was not limited to the known stretch-activated K2P channels, as K2P5.1 and
K2P18.1 currents were elevated by up to 15-fold and K2P1.1 currents were decreased 3-fold by
application of carvacrol. Furthermore, the influence of terpenes on K2P2.1 currents was found to
be: A. mediated by its carboxyl terminal, as its removal abolished their effect and B. indifferent
to phosphorylation of a conserved PKA site.
Our results demonstrate, for the first time, that terpenes are powerful modulators of K2P
potassium channels, that the nature of the effect is channel and terpene specific and that the
mechanism of action involves the C-terminus regulatory domain.